Improvements in Scrotal Thermoregulation in Patients with Varicoceles Treated by Using Traditional Korean Medicine: Two Case Reports.

A varicocele is a dilatation of the pampiniform venous plexus within the spermatic cord. The incidence of varicoceles is 15%, and it occurs in more than 40% of men in infertile couples. Traditional Korean medicine (TKM) has been used to treat male infertility in Korea. We present two cases of men with varicoceles diagnosed via physical examination and scrotal thermography. We treated these men for two months by using TKM techniques, which included acupuncture, pharmacopuncture, and herbal medicine. We used scrotal thermography to evaluate the varicoceles before and after TKM treatment. After TKM treatment, the scrotal thermoregulation of both patients improved. In Patient 1, the temperature difference between the left and the right pampiniform plexus (i.e., ΔTP) was 2.8°C before treatment. It decreased to 1.3°C after treatment. In addition, the temperature difference between the testicles (ΔTT) was 1.5°C before treatment; it decreased to 0.2°C after treatment. In Patient 2, the ΔTP was 1.5°C before treatment; it decreased to 0.2°C after treatment. This report is the first to show that TKM may be an option for treating patients with varicoceles, as determined by using a scrotal thermography evaluation.

Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases.

To investigate the clinicopathological and immunohistochemical features and prognostic factors for invasive extramammary Paget disease (EMPD) on penoscrotum, we described the clinical presentations, histopathology, and follow-up courses of 41 cases. The age of the patients ranged from 42 to 84 years. All the patients were treated with wide surgical excision, and 14 were confirmed to have lymph node metastasis. During follow-up, 18 patients (43.9%) developed local or distant recurrence, and 13 patients (31.7%) died of the disease. Histologically, glandular formation with true lumina within the epidermis was found in 29 cases, and signet ring cells were seen in 11 cases. In invasive components, nodular/micronodular growth pattern, glandular formation, and strands/solid sheets existed in 95.1% (39/41), 43.9% (18/41), and 24.4% (10/41) of the cases, respectively. More than half of the cases had at least 2 different types of invasive growth pattern. CK7 was diffusely positive in all cases, whereas CK20 was focally positive in 8 cases. GCDFP-15 was expressed to a variable degree in 24 cases. Presence of strands/solid sheets, lymphovascular invasion, and perineural invasion in invasive EMPD were found to be correlated with higher lymph node metastatic rate. Univariate analysis revealed that patients with one of the following prognostic factors: delay in diagnosis more than 7.5 years, depth of invasion more than 1 mm, invasive pattern of strands/solid sheets, marked inflammation, lymphovascular invasion, and lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Invasive pattern of strands/solid sheets is significantly associated with both lymph node metastasis and worse prognosis. Delay in diagnosis, depth of invasion, marked inflammation, lymphovascular invasion, and regional lymph node status are important prognostic factors.

Symplastic leiomyomas of the scrotum: a comparative study to usual leiomyomas and leiomyosarcomas.

Smooth muscle tumors of the scrotum are very uncommon, and those with degenerative-appearing atypia, variably designated as "atypical," "symplastic," or "bizarre" leiomyomas, are extremely rare with only 11 cases in the literature. Given their rarity, the diagnostic criteria and prognosis of symplastic leiomyomas are not well established. We describe 9 cases of scrotal symplastic leiomyomas and compare their histopathologic characteristics to 10 usual leiomyomas and 5 leiomyosarcomas of the scrotum. The preoperative diagnosis was scrotal tumor or cyst in all cases. The mean age was 46 years (range, 32 to 60 y) for usual, 59 (range, 48 to 79) for symplastic leiomyomas, and 57 (range, 49 to 65) for leiomyosarcoma. Submitting diagnoses for symplastic leiomyomas were: atypical spindle cell lesion (n=3); probably leiomyosarcoma (n=1); leiomyosarcoma (n=1); and none given (n=4). Symplastic leiomyomas were diagnosed when there was moderate-severe cytologic atypia, yet was degenerative-appearing with multinucleation or smudged chromatin in the setting of low nuclear/cytoplasmic ratio, low cellularity, and no mitotic activity. The mean size was 1.0 cm for usual leiomyomas, 1.0 cm for symplastic leiomyomas, and 2.0 cm for leiomyosarcomas. Leiomyosarcomas had high nuclear/cytoplasmic ratio, high cellularity, nuclear pleomorphism, and hyperchromasia. Five of 10 usual and 3/9 symplastic leiomyomas showed at least 1 ill-defined border simulating infiltrative growth. Three leiomyosarcomas were grade 1, and 2/5 were grade 2. Resection margins were positive in 5/10 usual and 3/9 symplastic leiomyomas and in 1/5 leiomyosarcoma. Ki67 labeling in usual leiomyomas was on average 2.4% (range, 1% to 5%) and in symplastic leiomyomas was 1.8% (range, 1% to 5%). Mitoses were absent in all cases of usual and symplastic leiomyomas. Mitotic figures averaged 4.7 (range, 1 to 7) and 13.5 (range, 7 to 20) per 10 HPF for the grade 1 and 2 leiomyosarcomas, respectively. None of the symplastic leiomyomas recurred after a median follow-up of 27 months. The 2 patients with grade 2 leiomyosarcoma had no evidence of metastases at 6 and 7 months follow-up, respectively. Scrotal symplastic leiomyomas may have an ill-defined infiltrative border, which along with their atypia mimic malignancy. Ki67 is low in symplastic leiomyomas, which along with their favorable follow-up and experience in other organs justifies a benign diagnosis. High cellularity and high mitotic activity are the most reliable features for the diagnosis of scrotal leiomyosarcoma.

Squamous neoplasia of the scrotum: a series of 29 cases.

The current epidemiology and clinicopathologic features of squamous cell carcinoma (SCC) of the scrotum are largely unknown because of its low incidence. We describe the histopathologic features, immunohistochemistry, and human papillomavirus (HPV) status of 29 patients with scrotal SCC. The mean age at presentation was 55 years (range, 30 to 74 y). White to black ratio was 1.9:1. There was no predominant occupation, with the majority being white-collar professionals. Clinical history of condylomas was present in 5 patients, and 7 patients had a history of multiple skin cancers including melanoma, basal cell carcinoma, and other SCCs. Other comorbidities included human immunodeficiency virus infection (n=2), kidney transplant (n=1), leukemia/lymphoma (n=2), hidradenitis suppurativa (n=1), chronic scrotal infections with abscess (n=1), inflamed epidermal inclusion cyst (n=1), and lichen planus (n=1). One patient had a history of regular tanning bed use. Morphologically, the majority was usual type (n=17), followed by basaloid (n=7) and warty (n=5). Nineteen cases were in situ, and 10 were invasive. Three patients had inguinal lymphadenopathy; in 1, metastasis was confirmed. Suprabasal nuclear staining for Ki67 was considered positive. For p16, a continuous band of nuclear and cytoplasmic staining was considered positive, and a noncontinuous or absence of staining was considered negative. p16 was positive in 10 cases; high-risk HPV was confirmed in 7 cases. Ki67 was positive in 8/17 (47%) usual, 6/7 (85.7%) basaloid, and 3/5 (60%) warty type. p53 was positive in 5/17 (29.4%) usual, 2/7 (28.6%) basaloid, and 1/5 (20%) warty type. All patients were treated with local excision only; 13 had positive margins. Three patients were treated with imiquimod after local excision. The median follow-up was 30 months. Three patients recurred and were treated with re-excision; 1 patient received radiotherapy. Overall, the morphologic, immunohistochemical, and HPV studies show that, similar to SCC of the vulva or penis, the SCC of the scrotum can be divided into 2 major groups. Group 1 (38.5%): positive for p16 and elevated Ki67. This group is associated with HPV infection and displays predominantly a basaloid or warty morphology, although a number of them are of usual type. Group 2 (61.5%): negative for p16. This group has variable Ki67 expression, is consistently negative for HPV, and displays predominantly usual-type morphology. SCC of the scrotum in the United States currently affects primarily white-collar professionals. The majority present with in situ lesions, and the high rate of positive margins at first excision suggests that they are clinically ill-defined lesions. No longer are occupational exposures to carcinogens the major etiology of scrotal SCC. Rather in contemporary times, common risk factors include HPV infection, immunocompromised states, and chronic scrotal inflammatory conditions.

Angiomyofibroblastoma-like tumor of the scrotum: a case report and review of literature.

Angiomyofibroblastoma-like tumor is a rare mesenchymal tumor of men. It commonly occurs during the fifth to eighth decades of life and mainly involves the inguinoscrotal region. It is derived from perivascular stem cells and has capacity of lipoid and myofibroblastic differentiation. Histopathologically this tumor in the male genitalia mimics female angiomyofibroblastoma but there are morphological and immunohistochemical differences between these lesions. We report a case of an angiomyofibroblastoma-like tumor that arose in the scrotal region in a 40-year-old man.

Clear cells of Toker in the developing anogenital region of male and female fetuses.

The clear cells of Toker are a mysterious population of intra-epidermal glandular cells. They were originally described in nipples, but were recently observed in the vulva as well. It was hypothesized that intra-epidermal embryonic remnants or underlying glands were a potential source. The embryological aspects were investigated by studying specimens of the anogenital region of 18 male and 15 female fetuses between 12 and 39 weeks gestation. The search for Toker cells was enhanced by cytokeratin (CK) 7 immunohistochemistry. The investigation showed that Toker cell elements are a normal, though highly variable constituent of the developing anogenital region. The study revealed the following: (1) single intra-epidermal glandular vesicles near follicular anlages in interlabial sulcuses of female fetuses of 15 and 16.5 weeks gestation; (2) CK7+ solitary cells, clusters, and vesicles which were related to developing intra-epidermal follicular canal tracks and tended to disperse inside the epidermis in fetuses of approximately 18 weeks gestation; (3) dispersed CK7+ cells in fetuses of 19-23 weeks gestation; (4) characteristic CK7+ Toker cell proliferations in fetuses more than 23 weeks gestation. These observations indicate that in the anogenital region, primordial follicular cells programmed to participate in the formation of apocrine and mammary-like glands, become displaced into the epidermis where they disperse, and proliferate into Toker cell populations. However, the proximity of Toker cells to CK7+ cells in excretory ducts of late fetal apocrine and mammary-like glands suggested a possible additional source. Consequences for Toker cells of the breast and primary Paget disease are discussed.

Three cases of sclerosing lipogranuloma: an immunohistochemical study.

Sclerosing lipogranuloma (SLG) is a rare disease that occurs in the male genital region. We report here three cases of SLG, including two of Y-shaped lesions in the penile base forming an intrascrotal mass, as well as a patient with a mass in the epidydimal region. All three lesions histologically exhibited formation of multiple granulomas consisting of multinucleated giant cells and epithelioid cells, in the fibroadipose tissue or around the epidydimis, in association with eosinophil infiltration. Membranocystic changes were found within the cytoplasm of multinucleated cells. In the two patients with scrotal lesions, membranocystic changes were positive for diastase-PAS reaction and on Sudan black B staining in dewaxed sections. CD68 staining was strongly positive in multinucleated giant cells and epithelioid cells. Most of the lymphocytes infiltrating the lesions were T cells associated with some S-100-positive dendritic cells. T-cell mediated immune reaction appears to be important in the histogenesis of SLG. The histogenesis is generally considered to be a foreign-body reaction to degenerated or damaged fatty tissue or lipids, but no apparent causative factors can be identified in some reported cases. All three patients in the present study had a good clinical course after biopsy or surgical excision. We thus report three cases of SLG including an unusual case in the epidydimal region, with some considerations regarding the histogenesis of SLG.

Scrotal calcinosis results from calcification of cysts derived from hair follicles: a series of 20 cases evaluating the spectrum of changes resulting in scrotal calcinosis.

Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The etiology of this entity is speculative largely as a result of the paucity of larger series.This study of 20 patients with scrotal calcinosis was undertaken to critically analyze the histology with a view to assess the probable etiology of this lesion. Two thirds of the patients were young adults. Of these, 11 patients (55%) were asymptomatic and 9 complained of symptoms related to the breakdown of these lesions (eg, discharge, itching, or heaviness in the scrotum). All cases showed classical histologic features of scrotal calcinosis with a variable amount of calcification in the dermis. In 14 cases the etiology of this calcification could be traced to originate from dilated epidermal cysts. The spectrum of changes probably started with the cystic dilation of the hair follicle, then calcification around and within this cyst. Finally the epithelial elements disappeared, leaving behind residual areas of calcification. The remaining 6 cases did not have epithelial cysts in the vicinity. Based on these observations we conclude that scrotal calcinosis results from calcification of hair follicular or epidermal cysts, but as most of the cases report, this epithelium disappears and may not be seen.

Cytochemical characterization of glycoconjugates in the apocrine glands of the equine scrotal skin.

Cytochemistry of glycoconjugates in the apocrine glands in the scrotal skin of the horse was studied using cytochemical methods for electron microscopy, particularly lectin cytochemistry. The secretory cells possessed a variable number of secretory vesicles, a well-developed Golgi apparatus, and abundant cisternae of the rough endoplasmic reticulum. Additionally, the basolateral plasma membrane formed numerous interdigitating folds. Glycoconjugates with vicinal diol groupings were present predominantly in the secretory vesicles, the Golgi apparatus, the surface coat of the plasma membrane, and the majority of the intracellular membranes. With lectin cytochemistry, the secretory vesicles of the glandular cells exhibited glycoproteins with different terminal sugars (alpha-D-mannose, beta-D-galactose beta-N-acetyl-D-glucosamine, and sialic acid). Several sugars were distinctly prominent in the surface coat of the plasma membrane of the secretory cells. The cytochemical properties of the complex glycoconjugates found are discussed in relation to the specific functions of the glandular secretions. These glands may have an important role in not only thermoregulation but protection of the scrotal skin, a specific body region.

Leiomyosarcoma of the paratesticular region: a clinicopathologic study.

The behavior of leiomyosarcoma (LMS) is site related, but there are limited data on such tumors presenting in the paratesticular region. Cases diagnosed as LMS of the paratesticular region from the files of three institutions were reviewed. Immunohistochemistry was performed in cases with available blocks, and follow-up information was obtained. From 31 cases originally diagnosed as LMS, 24 were retained after review. These were from men aged 34-86 years (mean 62 years; median 64 years) and involved the testicular tunica (10), spermatic cord (10), scrotal subcutis and dartos muscles (1 each), and the epididymis (1). Tumors ranged in size from 2-9 cm (mean 5 cm; median 4 cm). On immunohistochemical staining they expressed muscle-specific actin (13 of 14), smooth muscle actin (10 of 10), desmin (16 of 17), and CD34 (3 of 9); all of the latter three were strongly desmin-positive. Focal reactivity for cytokeratin (3 of 8) and S-100 protein (1 of 8) was seen. Follow-up information was available in 14 patients. Four (29%) had recurrences, in one case four times. Metastases to lymph nodes, lungs, or liver were seen in four patients (29%), of whom two had prior recurrences. Ten were alive with no evidence of disease (ANED), and four were dead of disease (DOD). Comparing outcome with tumor grade, all seven patients with grade 1 tumors (of whom two had recurrences) and all three with grade 2 tumors were ANED, whereas all four patients with grade 3 tumors were DOD. In summary, paratesticular LMSs are rare neoplasms. The majority in this site are low-grade, although high-grade lesions behave aggressively.

Immunohistochemical profile of primary sclerosing lipogranuloma of the scrotum: report of five cases.

Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed common histological features: a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophage/monocytes in the interstitium. Immunohistochemistry disclosed the epithelioid cells and multinucleated giant cells of the granuloma to be monocytes in nature, as both types of cells were positive for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and S-100 protein positive Langerhans-like cells were frequently found. S-100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.

Verruciform xanthoma: an immunocytochemical study.

Verruciform xanthoma is a rare lesion that occurs predominantly on the oral mucosae, but also on other mucosal sites and on the skin. We report an immunocytochemical analysis of the xanthoma cells in three cases of verruciform xanthoma (two vulval and one scrotal), and also attempt to identify human papilloma virus (HPV) as a possible trigger for the production of these lesions. We employed a panel of seven histiocytic markers (CD68 [KP1], KiM1P, HAM 56, lysozyme, vimentin, peanut agglutinin and factor X111a) and two others to identify HPV involvement (CAMVIR-1 and bovine papilloma virus-1 [BPV-1]). Results showed the xanthoma cells to be positive for CD68, KiM1P, HAM 56 and vimentin, with less consistent labelling for peanut agglutinin and lysozyme. CAMVIR-1 and BPV-1 were negative in all three cases. These findings support the view that the xanthoma cells are derived from a monocyte macrophage lineage and fail to demonstrate HPV as the cause.

Sclerosing lipogranuloma of the male genitalia: analysis of the lipid constituents and histological study.

An analysis of lipids and histological examination were performed on tissues resected from 2 patients with sclerosing lipogranuloma of the scrotum. The clinical course and histological characteristics were consistent with those reported previously for typical primary sclerosing lipogranuloma of the male genitalia. There was no history of the injection or topical application of oils or fats. Both of our patients had eosinophilia and the lesions showed eosinophilic infiltration. Complete natural regression occurred several months after partial resection of the lesion in both cases, and no recurrence has been noted during follow-up. This lipid analysis and histological study revealed that no exogenous fatty elements were present and suggested that degeneration of endogenous fat due to some allergic mechanism might be involved in the development of sclerosing lipogranuloma. The eosinophilia associated with this disease and its spontaneous regression after partial resection also support this assumption.

Demonstration of calcitonin gene-related peptide receptors in the gubernaculum by computerized densitometry.

The gubernaculum appears to guide inguinoscrotal testicular descent by migration into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) has been found in the scrotal branches of the genitofemoral nerve of neonatal rats, and is known to stimulate gubernacular motility in vitro. This study aimed to identify CGRP receptors in the gubernaculum, which should be present if CGRP mediates gubernacular migration toward the scrotum. Gubernacular sections from neonatal male rats were incubated with [125I]-human CGRP as well as a variety of unlabeled neuropeptides. By using computerized densitometry, the quantitation of CGRP binding derived from in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. The binding analysis showed a single class of sites with a dissociation constant (Kd) of 2.13 nmol/L and a receptor density of 27.4 fmol/mg polymer. These results endorse the hypothesis that CGRP released from the nerve acts directly on the cremaster via its own receptors, which have not been described previously.

Idiopathic scrotal calcinosis is idiopathic.

The appearance of calcific masses within the dermis of scrotal skin is generally referred to as idiopathic scrotal calcinosis. There has been some debate about the pathogenesis of these calcium deposits. This debate centers on the question of whether the calcium deposition is truly idiopathic or whether it occurs as a result of preexisting epidermal cysts. We have performed immunohistochemical staining for keratin in nine patients with apparent idiopathic scrotal calcinosis and have found no evidence of keratin in the dermal tissue immediately adjacent to the calcium deposits. We conclude that idiopathic scrotal calcinosis is idiopathic.